Serum small extracellular vesicles promote M1 activation of microglia after cerebral ischemia/reperfusion injury


Posted: 2021-11-05 19:00:00
Neurosci Lett . 2021 Nov 1;136307. doi: 10.1016/j.neulet.2021.136307. Online ahead of print. Affiliations Expand Affiliations 1 Institute of Immunology, College of Life science and Technology, Jinan University, Guangzhou 510632, China; The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang 524023, China. 2 Institute of Immunology, College of Life science and Technology, Jinan University, Guangzhou 510632, China. 3 The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China. 4 Institute of Immunology, College of Life science and Technology, Jinan University, Guangzhou 510632, China. Electronic address: tjyh@jnu.edu.cn. 5 Department of Neurology, Affiliated Hospital of Nantong University, Nantong 226019, China. Electronic address: jiqiuhong@ntu.edu.cn. Item in Clipboard Xin Zhou et al. Neurosci Lett. 2021. Show details Display options Display options Format Neurosci Lett . 2021 Nov 1;136307. doi: 10.1016/j.neulet.2021.136307. Online ahead of print. Affiliations 1 Institute of Immunology, College of Life science and Technology, Jinan University, Guangzhou 510632, China; The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang 524023, China. 2 Institute of Immunology, College of Life science and Technology, Jinan University, Guangzhou 510632, China. 3 The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China. 4 Institute of Immunology, College of Life science and Technology, Jinan University, Guangzhou 510632, China. Electronic address: tjyh@jnu.edu.cn. 5 Department of Neurology, Affiliated Hospital of Nantong University, Nantong 226019, China. Electronic address: jiqiuhong@ntu.edu.cn. Item in Clipboard CiteDisplay options Display options Format Abstract Microglial M1 activation is detrimental to stroke outcomes. Recent studies have shown that circulating small extracellular vesicles (sEVs) can deliver miRNAs to target cells and regulate recipient cell functions. Herein, we tested the hypothesis that miRNA delivery by serum sEVs after cerebral ischemia/reperfusion (I/R) injury promote microglial M1 activation, demonstrating that serum sEVs from middle cerebral artery occlusion (MCAO) mice promoted proliferation and M1 activation of BV2 microglia. To explore the underlying mechanism of serum sEVs-mediated microglial activation in the early phase of cerebral I/R injury, we examined the effects of ischemic brain injury on the serum sEVs miRNAs profile in a mouse MCAO model using small RNAseq. Of the 1,257 detected miRNA replications, the levels of 72 were significantly modulated. Bioinformatics analysis revealed that a panel of miRNAs was closely associated with inflammation, and in vitro experiments demonstrated that serum sEVs from MCAO mice could effectively transfer inflammatory miRNAs to BV2 microglia. Collectively, our data suggested that miRNAs delivered by serum sEVs after cerebral I/R injury promoted microglial M1 activation. The identification of microglial activation regulators in future studies will give rise to more effective treatments for stroke. Keywords: Activation; Cerebral ischemia/reperfusion; MiRNAs; Microglia; Serum small extracellular vesicles. Copyright © 2021. Published by Elsevier B.V. Conflict of interest statement Conflict of Interest The authors declare that they have no competing interests [x] Cite Copy Format: Send To [x]

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